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ENIGMA MDD working group

ENIGMA MDD working group. Teleconference 20 th of September 2016 2 PM CET, 3 PM CEST, 11 PM AEST, 6 AM PDT. Agenda. New project proposals Progress secondary projects (un)mute your line by pressing 16!!. Overall status sites. link to spreadsheet. link to analysis plan.

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ENIGMA MDD working group

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  1. ENIGMA MDD working group Teleconference 20th of September 2016 2 PM CET, 3 PM CEST, 11 PM AEST, 6 AM PDT

  2. Agenda • New project proposals • Progress secondary projects (un)mute your line by pressing 16!!

  3. Overall status sites link to spreadsheet link to analysis plan link to project specific table with status of each site

  4. Project specific spreadsheet

  5. Agenda • New project proposals - ENIGMA MDD Lifespan project: normative modelling - ENIGMA MDD Asymmetry project • Progress secondary projects

  6. MDD lifespan mega-analysis Aim: Investigate the association between MDD and subcortical and cortical brain structure across the life span and examine the impact of clinical characteristics in more detail. Measures: • LandRvolumes.csv • CorticalMeasuresENIGMA.csv • CorticalMeasuresENIGMA.csv • Covariates.csv • => resulting from subcortical and cortical QA protocols

  7. Normative modeling analysis plan proposal (using Gaussian Process Regression)

  8. Agenda • New project proposals - ENIGMA MDD Lifespan project: normative modelling - ENIGMA MDD Asymmetry project • Progress secondary projects

  9. Agenda • New project proposals • Progress secondary projects: - Standardizing severity questionnaires (Felix Fischer/Matthias Rose) - MDD DTI project (Sinead Kelly/Laura van Velzen) - MDD Hippocampal subfields project (Philipp Saemann) - MDD Shape project (Boris Gutman) - MDD Insomnia project (Eus van Someren/Lianne Schmaal/Dick Veltman) - MDD Machine learning project (Paul Thompson) - MDD Childhood Trauma project (Thomas Frodl) - MDD Suicidality project (Miguel Renteria)

  10. Agenda • New project proposals • Progress secondary projects: - Standardizing severity questionnaires (Felix Fischer/Matthias Rose) - MDD DTI project (Sinead Kelly/Laura van Velzen) - MDD Hippocampal subfields project (Philipp Saemann) - MDD Shape project (Boris Gutman) - MDD Insomnia project (Eus van Someren/Lianne Schmaal/Dick Veltman) - MDD Machine learning project (Paul Thompson) - MDD Childhood Trauma project (Thomas Frodl) - MDD Suicidality project (Miguel Renteria)

  11. ENIGMA MDD-DTI

  12. Agenda • New project proposals • Progress secondary projects: - Standardizing severity questionnaires (Felix Fischer/Matthias Rose) - MDD DTI project (Sinead Kelly/Laura van Velzen) - MDD Hippocampal subfields project (Philipp Saemann) - MDD Shape project (Boris Gutman) - MDD Insomnia project (Eus van Someren/Lianne Schmaal/Dick Veltman) - MDD Machine learning project (Paul Thompson) - MDD Childhood Trauma project (Thomas Frodl) - MDD Suicidality project (Miguel Renteria)

  13. ENIGMA-MDDhippocampalsubfieldsprojectCurrentbottleneck: QCstep • Review of an extensive set of 1.5 T and 3 T cases demonstrated: • Discontinuities of CA1/subiculum often are often • caused by rigid axial/coronal slicing of complex 3D structures. • ‚Dynamic viewing‘ using Freeview recommended for >10 • examplary cases in own dataset, using e. g.: • freeview nu.gz left_discreteLabels.mgz • Preliminary conclusions so far: • Volumetric effects of minor deviations should be rather small (analysis ongoing) • Many ‚minor‘ at-first-sight problems need no exclusion • Still, dummy covariates can be produced for 5 of 9 subregions (analysis with covariates, • w/o covariates, and with exclusion) • Incomplete coverage of the subfield segmentation: potential influence on result. • Four simple search tools will be distributed in a script based on the full set of variables:

  14. ENIGMA-MDDhippocampalsubfieldsprojectDiverse automatedtoolstodetectedpotentiallyartifact-relatedpatterns • Grossdiscorrelationbetweenrecon-all basedHV (subcorticalsegmentation) andsumof all • subregions, givenrecon-all hasbeenQCed: • Example: • 2. Outliers per subfield(after ICVnormalisationofvalues) • 3. Strong left/rightasymmetryindexfor a subregion • 4. Shiftoftypicallyobservedvolumetricorderofsubregions(seenextslide)

  15. ENIGMA-MDDhippocampalsubfieldsprojectSome simple algorithmstodetectedpotentiallyartefact-relatedpatterns *nearly 100% rank #4 Presubiculum GCMLDG CA4 CA3 Fissure CA1 ML Tail Subiculum* „Disturbed ranking score“ CA1 not largest 1 pt. ML (very stable) not considered Tail dropped below rank #3 1 pt. Subiculum not rank #4 1 pt. Regions 5-6  2 ranks shifted (each) 1 pt. Regions 7  1 rank shifted 1 pt. Regions 8-9  1 ranks shifted 0.5 pt. Regions 10-12 not considered ------------------------------------------------------------- Sum score:  2 points as indicator of potentially artefactual volume shifts Automatedidentificationof ~10% cases withsomealtered internal structure

  16. ENIGMA-MDDhippocampalsubfieldsprojectNext steps Output frommethod 4 is a listofcasesforvisualreviewand optional definitionofdummymarker • Next steps: • Feedback for several specific QC questions needed from selected centers (contacted through @) • Circulation of QC support script and instructions for as-simple-as possible visual followup… • Run local analysis (R script) • New centers interested? Participation possibe if general FreeSurfer • segmentation and QC (cortex and subcortical structures) has been performed. • NB: Freesurfer v5.3 plus v6.0 (sufields) combinable in this case!

  17. Agenda • New project proposals • Progress secondary projects: - Standardizing severity questionnaires (Felix Fischer/Matthias Rose) - MDD DTI project (Sinead Kelly/Laura van Velzen) - MDD Hippocampal subfields project (Philipp Saemann) - MDD Shape project (Boris Gutman) - MDD Insomnia project (Eus van Someren/Lianne Schmaal/Dick Veltman) - MDD Machine learning project (Paul Thompson) - MDD Childhood Trauma project (Thomas Frodl) - MDD Suicidality project (Miguel Renteria)

  18. ENIGMA MDD Shape 15 Sites 1991 Patients, 3270 Controls

  19. MDD Shape updates – 9/19 • Both SHIP datasets shape QC finished (by IGC RA’s) – will send • Folks running meta-analysis, please download and run the R-scripts, found here inside tar.gz: http://bit.ly/1RSoUyP. Please follow the 1-page instructions – should be easy. Big thanks to Lianne for testing it thoroughly • Still time to join if you haven’t yet. Either meta-analysis or individual data sharing (or a mix) are possible

  20. ENIGMA Shape Support Download link for ENIGMA Shape Tools: http://enigma.usc.edu/protocols/imaging-protocols/ Core Support Team – USC Imaging Genetics Center: Boris Gutman – shape project lead bgutman@usc.edu Chris Ching – shape project coordinator cching47@gmail.com Arvin Saremi – shape quality control asaremi@usc.edu Dmitry Isaev – shape statistics dizzymiracle@gmail.com Off-site ENIGMA shape support: ENIGMA-MDD: Sean Hatton, UCSD sehatton@ucsd.edu ENIGMA-Schizophrenia: Kate Alpert, Northwestern University k-alpert@northwestern.edu

  21. Agenda • New project proposals • Progress secondary projects: - Standardizing severity questionnaires (Felix Fischer/Matthias Rose) - MDD DTI project (Sinead Kelly/Laura van Velzen) - MDD Hippocampal subfields project (Philipp Saemann) - MDD Shape project (Boris Gutman) - MDD Insomnia project (Eus van Someren/Lianne Schmaal/Dick Veltman) - MDD Machine learning project (Paul Thompson) - MDD Childhood Trauma project (Thomas Frodl) - MDD Suicidality project (Miguel Renteria)

  22. Project MDD INSOMNIA

  23. Agenda • New project proposals • Progress secondary projects: - Standardizing severity questionnaires (Felix Fischer/Matthias Rose) - MDD DTI project (Sinead Kelly/Laura van Velzen) - MDD Hippocampal subfields project (Philipp Saemann) - MDD Shape project (Boris Gutman) - MDD Insomnia project (Eus van Someren/Lianne Schmaal/Dick Veltman) - MDD Machine learning project (Paul Thompson) - MDD Childhood Trauma project (Thomas Frodl) - MDD Suicidality project (Miguel Renteria)

  24. ENIGMA_MDD (Machine Learning) Project Coordinator: *Dr. Dajiang Zhu (dajiang.zhu@gmail.com) * Mr. Marc B. Harrison (marc.harrison@loni.usc.edu) * Prof. Paul Thompson (pthomp@usc.edu) * USC Imaging Genetics Center, Marina del Rey, CA IGC

  25. Motivation ENIGMA has not attempted machine learning analyses that combine information from multiple ROIs to distinguish patients and controls. Machine learning can use a variety of different mathematical approaches to learn which MRI features can be combined to best distinguish patients and controls • We propose to test two methods: • multi-site LASSO (Li et al., 2016) • EPIC (Prasad et al. 2014, 2016) IGC

  26. Progress – 09/20/2016 IGC

  27. SIPAIM 2016 - Submitted Cortical thickness measures in these 30 regions were retained by a distributed machine learning model for classifying individuals as having major depression or not. Corresponding brain areas in each hemisphere are shown with the same color. The retention of limbic regions is in line with expectation, and consistent with the symptoms of depressed mood in MDD. Summary of classification results IGC

  28. Initial EPIC Results using cortical thickness Table 1 N=1482 (control 889, patient 593) These values were constructed using cortical thickness values, and an R package called Amelia for imputing missing values. Five regions of interest were removed due to missing over 10% of the data. Future directions will apply this methodology to surface average and subcortical volume. IGC

  29. Agenda • New project proposals • Progress secondary projects: - Standardizing severity questionnaires (Felix Fischer/Matthias Rose) - MDD DTI project (Sinead Kelly/Laura van Velzen) - MDD Hippocampal subfields project (Philipp Saemann) - MDD Shape project (Boris Gutman) - MDD Insomnia project (Eus van Someren/Lianne Schmaal/Dick Veltman) - MDD Machine learning project (Paul Thompson) - MDD Childhood Trauma project (Thomas Frodl) - MDD Suicidality project (Miguel Renteria)

  30. Agenda Next conference call in October/November, hopefully with new results to show from the different projects!

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